OBJECTIVES: The objective of this research was to determine the incremental cost-effectiveness, from a US societal perspective, of adding temozolomide to the previous standard of care (radiotherapy only) for the adjuvant treatment of newly diagnosed glioblastoma.  METHODS: A Markov model with a one-month cycle length and five-year time horizon was constructed in Microsoft Excel. All model parameters were obtained from relevant peer-reviewed literature based on systematic review. Transition probabilities were calculated using survival data from randomized controlled trials comparing temozolomide plus radiotherapy versus radiotherapy alone. Direct and indirect costs were derived from published peer-reviewed literature or government data. Utilities were obtained from a previously published cost-utility analysis of temozolomide and carmustine wafers in newly diagnosed glioblatoma.  Univariate and threshold sensitivity analyses were conducted on all survival data, input costs, utilities, and other important parameters.  RESULTS: The addition of temozolomide to the standard radiotherapy regimen was associated with a base-case incremental cost-effectiveness ratio of $154,933 per quality-adjusted life-year. This is considerably higher than the only other comparable estimate, which assumed the perspective of the UK National Health Service and did not include indirect costs. The model was most sensitive to the utility associated with the use of temozolomide during the maintenance phase of stable disease treatment.  CONCLUSIONS: The base-case incremental cost-effectiveness ratio lies just beyond a willingness-to-pay threshold of $150,000 per quality-adjusted life-year. However, sensitivity analysis revealed numerous plausible scenarios that produced lower estimates. Notably, a 10% increase in the utility associated with stable disease treatment produced an estimate of $120,743 per quality-adjusted life-year. Given these results and the lack of alternative treatments for glioblastoma, we conclude that temozolomide’s use in this setting is not definitively cost-effective. However, better estimates of relevant health state utilities could greatly improve cost-effectiveness models for glioblastoma treatments.